Previous evidence supported that the ER-stress-induced unfolded protein responses (UPRs) are essential steps in diabetes mediated neurotoxicity and cognitive impairment (Lind et al., 2013; Zhang et al., 2013; Zhao et al., 2015; Kong et al., 2018); the ER stress markers (ATF4, GRP78, ATF6, P-PERK, XBP-1s) are all increased both in the hippocampus and cortex in the animal model of diabetes. This evidence concerns the gene HSPA5 and diabetes mellitus.